Studies of lysozyme have played a major role over several decades in defining the general principles underlying protein structure, folding, and stability. Following the discovery some 10 years ago that ... [more ▼]

Studies of lysozyme have played a major role over several decades in defining the general principles underlying protein structure, folding, and stability. Following the discovery some 10 years ago that two mutational variants of lysozyme are associated with systemic amyloidosis, these studies have been extended to investigate the mechanism of amyloid fibril formation. This Account describes our present knowledge of lysozyme folding and misfolding, and how the latter can give rise to amyloid disease. It also discusses the significance of these studies for our general understanding of normal and aberrant protein folding in the context of human health and disease. [less ▲]

Normal and shear forces were measured as a function of surface separation, D, between hydrophobized mica surfaces bearing layers of a hydrophobic−polyelectrolytic diblock copolymer, poly(methyl methacrylate)-block-poly(sodium sulfonated glycidyl methacrylate) copolymer (PMMA-b-PSGMA). The copolymers were attached to each hydrophobized surface by their hydrophobic PMMA moieties with the nonadsorbing polyelectrolytic PSGMA tails extending into the aqueous medium to form a polyelectrolyte brush. Following overnight incubation in 10−4 w/v aqueous solution of the copolymer, the strong hydrophobic attraction between the hydrophobized mica surfaces across water was replaced by strongly repulsive normal forces between them. These were attributed to the osmotic repulsion arising from the confined counterions at long-range, together with steric repulsion between the compressed brush layers at shorter range. The corresponding shear forces on sliding the surfaces were extremely low and below our detection limit (±20−30 nN), even when compressed down to a volume fraction close to unity. On further compression, very weak shear forces (130 ± 30 nN) were measured due to the increase in the effective viscous drag experienced by the compressed, sliding layers. At separations corresponding to pressures of a few atmospheres, the shearing motion led to abrupt removal of most of the chains out of the gap, and the surfaces jumped into adhesive contact. The extremely low frictional forces between the charged brushes (prior to their removal) is attributed to the exceptional resistance to mutual interpenetration displayed by the compressed, counterion-swollen brushes, together with the fluidity of the hydration layers surrounding the charged, rubbing polymer segments. [less ▲]

The diblock copolymer poly(methyl methacrylate)-b-poly(sodium sulfonated glycidyl methacrylate) (PMMA-b-PSGMA) was end-attached by its hydrophobic block (PMMA) onto mica hydrophobized by a stearic trimethylammonium iodide (STAI) layer, to form a polyelectrolyte brush immersed in water. With a surface force balance (SFB), we extended earlier measurements between two such brush layers for the case of normal and shear forces at different shear rates, surface separation, and compressions between one mica surface coated with STAI or a STAI-diblock layer against a bare mica surface. After coating one of the surfaces with STAI, a long range attraction that results in a jump into an adhesive flat contact between the hydrophobic and hydrophilic surfaces was observed. A very different behavior was seen after forming the polyelectrolyte brush on the STAI-coated surface. The long range attraction was replaced by repulsion, accompanied by very low friction during shear (ca. three orders of magnitude lower than with adsorbed polyelectrolytes). On further compression, a weak attraction to the adhesive contact was observed. From the final surface-surface contact separation, we deduce that most of the polyelectrolyte diblock brush layer was squeezed out from the gap, leaving the STAI layer and a small amount of the polymer attached to the surface. Stick-sliding behavior was seen while applying shear, suggesting a dissipation mechanism caused by the trapped polyelectrolyte. [less ▲]

This study derives normal values for electro- and vectorcardiographic parameters, as generated by the Holmes semi-orthogonal lead system, in healthy growing calves. Sixty-four electrocardiograms were ... [more ▼]

This study derives normal values for electro- and vectorcardiographic parameters, as generated by the Holmes semi-orthogonal lead system, in healthy growing calves. Sixty-four electrocardiograms were recorded from healthy Friesian calves aged from one week to one year. Waveform and duration were analysed and compared in the X-, Y- and Z-leads. The modal P, QRS and T tridimensional vectors were graphically constructed and their magnitude and orientation were calculated. The duration of waves and intervals were similar to data previously reported in the bovine species. Differences from data reported in other species were attributed to heart rate. The duration of waves and QT and ST intervals significantly lengthened with the decrease in heart rate which occurred during growth. PR interval significantly lengthened with physical maturation, and this change was independent of the decrease in heart rate. The magnitude and the orientation of the spatial modal vectors were approximately similar to the few data previously reported in cattle and in other ungulates and were not affected by somatic growth [less ▲]

Puberty is unique in the sense that its onset shows an extraordinary individual variability of about 5 years, the basis of which being still elusive despite research efforts to understand the reason why ... [more ▼]

Puberty is unique in the sense that its onset shows an extraordinary individual variability of about 5 years, the basis of which being still elusive despite research efforts to understand the reason why. Continuing changes in environmental influences and interaction with genetic determinants are suggested by the still evolving pattern of the pubertal process both clinically and mechanistically. For instance, secular trends towards earlier breast development have been observed during the two past decades in some countries, resulting in possible skewing of the age distribution of that pubertal sign with less obvious changes in menarcheal age. Conceptually, puberty and subsequent reproduction appear now to be influenced by conditions not only at the time when they occur, but also during fetal and perinatal life. In addition, these influences can be apparently opposing since early maturation follows fetal malnourishment and postnatal overfeeding. In this review, the semiology and pathophysiology of puberty are discussed in a lifelong developmental perspective. [less ▲]

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2002), 38(1), 77-86

We investigated the mere exposure effect and the explicit memory in Alzheimer's disease (AD) patients and elderly control subjects, using unfamiliar faces. During the exposure phase, the subjects ... [more ▼]

We investigated the mere exposure effect and the explicit memory in Alzheimer's disease (AD) patients and elderly control subjects, using unfamiliar faces. During the exposure phase, the subjects estimated the age of briefly flashed faces. The mere exposure effect was examined by presenting pairs of faces (old and new) and asking participants to select the face they liked. The participants were then presented with a forced-choice explicit recognition task. Controls subjects exhibited above-chance preference and recognition scores for old faces. The AD patients also showed the mere exposure effect but no explicit recognition. These results suggest that the processes involved in the mere exposure effect are preserved in AD patients despite their impaired explicit recognition. The results are discussed in terms of Seamon et al.'s (1995) proposal that processes involved in the mere exposure effect are equivalent to those subserving perceptual priming. These processes would depend on extrastriate areas which are relatively preserved in AD patients. [less ▲]

Classically, mutations in the DAX-1 gene cause an adrenal hypoplasia congenita associated with adrenal insufficiency and hypogonadotrophic hypogonadism. However, mini-puberty onset seems to be normal in ... [more ▼]

Classically, mutations in the DAX-1 gene cause an adrenal hypoplasia congenita associated with adrenal insufficiency and hypogonadotrophic hypogonadism. However, mini-puberty onset seems to be normal in those patients suggesting a normal function of the pituitary-gonadal axis during the perinatal period. [less ▲]

Objective: Measurements of the variability in heart rate are increasingly used as markers of cardiac autonomic activity. We sought to establish the development this variability in healthy young infants ... [more ▼]

Objective: Measurements of the variability in heart rate are increasingly used as markers of cardiac autonomic activity. We sought to establish the development this variability in healthy young infants while sleeping. Patients: We carried out polygraphic studies with electrocardiographic recording in 587 healthy infants aged from 5 to 26 weeks. Methods: We determined several variables over a period of 400 minutes sleeping: mean RR interval, 5 time-domain (SDNN, SDNNi, SDANNi, RMSSD, and pNN50) and 5 frequency-domain indexes (spectral power over 3 regions of interest, total power and low-to-high frequency ratio). Frequency-domain indexes were also assessed separately for the periods of quiet sleep and those of rapid eye movement sleep. Results: Our data showed a significant correlation between the indexes of heart rate variability and the mean RR interval, the breathing rate, and the corrected age of the infants. We also demonstrated the importance of the maturation of the sleeping patterns. Conclusion: These data in a large cohort of healthy infants confirm a progressive maturation of the autonomic nervous system during sleep, and may be used to examine the influence of physiological and pathophysiological factors on autonomic control during polygraphic studies. [less ▲]

BACKGROUND: Availability of normative reference values for cardiac chamber dimensions, volumes, mass, and function is a prerequisite for the accurate application of echocardiography for both clinical and ... [more ▼]

BACKGROUND: Availability of normative reference values for cardiac chamber dimensions, volumes, mass, and function is a prerequisite for the accurate application of echocardiography for both clinical and research purposes. However, due to the lack of consistency in current echocardiographic 'reference values', their use for clinical decision-making remains questionable. AIMS: The aim of the 'Normal Reference Ranges for Echocardiography Study (NORRE Study)' is to obtain a set of 'normal values' for cardiac chamber geometry and function in a large cohort of healthy Caucasian individuals aged over a wide range of ages (25-75 years) using both conventional and advanced echocardiographic techniques. METHODS: The NORRE Study is a large prospective, observational multicentre study in which transthoracic echocardiographic studies will be acquired in 22 laboratories accredited by the European Association of Cardiovascular Imaging and in one laboratory in the USA accredited by ICAEL. The final sample size has been estimated in 1100 normal subjects in whom M-mode, 2D, and 3D imaging, colour Doppler, pulsed-wave Doppler, pulsed-wave tissue Doppler, and colour tissue Doppler imaging data will be obtained. All studies will be sent to a central echocardiographic core laboratory for quantitative analysis. Multiple studies will be performed for reproducibility analysis. CONCLUSION: After completion of the NORRE Study, uniform reference limits according to age, gender, and anthropometric parameters will be available to standardize the quantitative interpretation of echocardiography. [less ▲]

In nephrology, chronic kidney disease is defined by both proteinuria and measurement of glomerular filtration rate (GFR). This article focuses on GFR and different ways to define its normal reference ... [more ▼]

In nephrology, chronic kidney disease is defined by both proteinuria and measurement of glomerular filtration rate (GFR). This article focuses on GFR and different ways to define its normal reference values. In this context, we compare two perspectives: first the reference values defined by measuring GFR in normal individuals (the 'classical way') and secondly a fixed cut-off value at 60 mL/min/1.73 m(2) according to the associated mortality risk (the 'prognostic way'). Following the classical way, we can assert that normal GFR values are largely over 60 mL/min/1.73 m(2) in healthy subjects, at least before the age of 70 years. However, we know that GFR physiologically decreases with age, and in adults older than 70 years, values below 60 mL/min/1.73 m(2) could be considered normal. Following the 'prognostic way', the fixed cut-off of 60 mL/min/1.73 m(2) has been retained in the K-DIGO guidelines. However, we challenge this concept and the fact that the variable 'age' is poorly taken into account in these data. There is an obvious discrepancy between the reference values defined either by the 'classical way' or by the 'prognostic way' which we think could be largely reduced, if age was better taken into consideration in these definitions. [less ▲]